Mediron

Rating: 5 - 1 review(s)
What are the side effects you encounter while taking this medicine?
advertisement

Mediron uses

Mediron consists of Econazole Nitrate, Fluocinolone Acetonide, Gentamicin Sulfate.

Econazole Nitrate:


1 INDICATIONS AND USAGE

Mediron (Econazole Nitrate) (econazole nitrate) topical foam, 1%, is indicated for the treatment of interdigital tinea pedis caused by Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum in patients 12 years of age and older.

Mediron (Econazole Nitrate) is an azole antifungal indicated for the treatment of interdigital tinea pedis caused by Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum in patients 12 years of age and older. (1)

2 DOSAGE AND ADMINISTRATION

Mediron (Econazole Nitrate) topical foam, 1% is for topical use only. Mediron (Econazole Nitrate) topical foam, 1% is not for oral, ophthalmic, or intravaginal use.

Mediron (Econazole Nitrate) topical foam, 1% should be applied to cover affected areas once daily for 4 weeks.

  • For topical use only; not for oral, ophthalmic, or intravaginal use. (2)
  • Apply once daily for 4 weeks. (2)

3 DOSAGE FORMS AND STRENGTHS

Foam, 1%. Each gram of Mediron (Econazole Nitrate) topical foam, 1%, contains 10 mg of Mediron (Econazole Nitrate) in a white to off-white foam.

Foam, 1%. (3)

4 CONTRAINDICATIONS

None.

None. (4)

5 WARNINGS AND PRECAUTIONS

Contents are flammable. Instruct the patient to avoid heat, flame, and/or smoking during and immediately following application.

5.1 Flammability

Mediron (Econazole Nitrate) topical foam is flammable. Avoid heat, flame, and smoking during and immediately following application. Contents under pressure. Do not puncture and/or incinerate the containers. Do not expose containers to heat and/or store at temperatures above 120°F (49°C) even when empty. Do not store in direct sunlight.

advertisement

6 ADVERSE REACTIONS

During clinical trials with Mediron topical foam, the most common adverse reactions were application site reactions which occurred in less than 1% of subjects in both the Mediron (Econazole Nitrate) and vehicle arms. (6)

To report SUSPECTED ADVERSE REACTIONS, contact Exeltis USA Dermatology, LLC. at 1-877-324-9349 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In two double-blind, vehicle-controlled clinical trials, 495 subjects were exposed to Mediron (Econazole Nitrate) topical foam or vehicle (246 subjects were exposed to Mediron (Econazole Nitrate) topical foam, 1% and 249 were exposed to vehicle). Subjects with interdigital tinea pedis applied foam or vehicle once daily for approximately 28 days. During clinical trials with Mediron (Econazole Nitrate) topical foam, the most common adverse reactions were application site reactions which occurred in less than 1% of subjects in both the Mediron (Econazole Nitrate) and vehicle arms.

7 DRUG INTERACTIONS

7.1 Warfarin

Concomitant administration of econazole and warfarin has resulted in enhancement of anticoagulant effect. Most cases reported product application with use under occlusion, genital application, or application to a large body surface area which may increase the systemic absorption of Mediron (Econazole Nitrate). Monitoring of International Normalized Ratio (INR) and/or prothrombin time may be indicated especially for patients who apply econazole to large body surface areas, in the genital area, or under occlusion.

advertisement

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C

There are no adequate and well-controlled trials with Mediron topical foam in pregnant women. Mediron (Econazole Nitrate) topical foam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Mediron (Econazole Nitrate) has not been shown to be teratogenic when administered orally to mice, rabbits or rats. Fetotoxic or embryotoxic effects were observed in Segment I oral studies with rats receiving 10 to 40 times the human dermal dose. Similar effects were observed in Segment II or Segment III studies with mice, rabbits and/or rats receiving oral doses 80 or 40 times the human dermal dose.

8.3 Nursing Mothers

It is not known whether Mediron (Econazole Nitrate) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Mediron (Econazole Nitrate) is administered to a nursing woman. Following oral administration of Mediron (Econazole Nitrate) to lactating rats, econazole and/or metabolites were excreted in milk and were found in nursing pups.

8.4 Pediatric Use

Of the 173 subjects treated with Mediron topical foam, 1% in the clinical trials, 2 subjects were 12-17 years old. In a pediatric maximal use trial, Mediron (Econazole Nitrate) topical foam, 1% was applied once daily to eighteen subjects aged 12 to 17 years with interdigital tinea pedis for 28 days [see Clinical Pharmacology (12.3) ]. The safety findings for subjects 12 to 17 years were similar to those in adult population.

8.5 Geriatric Use

Of the 173 subjects treated with Mediron (Econazole Nitrate) topical foam, 1% in the adult clinical trials, 6 subjects were 65 years or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.

advertisement

11 DESCRIPTION

Mediron (Econazole Nitrate) (econazole nitrate) topical foam, 1% contains the azole antifungal agent, Mediron (Econazole Nitrate) in an oil-in-water emulsion base consisting of the following inactive ingredients: dimethicone, glycerin, polysorbate 20, povidone, propylene glycol, stearic acid, trolamine, purified water and butane as a propellant. Each gram of Mediron (Econazole Nitrate) topical foam, 1% contains 10 mg of Mediron (Econazole Nitrate), USP, in a white to off-white foam. Mediron (Econazole Nitrate) topical foam, 1% is alcohol (ethanol)-free and for topical use only.

Chemically, Mediron (Econazole Nitrate) is 1-[2-{(4-chloro-phenyl)methoxy}-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole mononitrate. Mediron (Econazole Nitrate) has the molecular formula C18H15Cl3N2O.HNO3 and a molecular weight of 444.70. Its molecular structure is as follows:

chem structure

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Mediron topical foam is an azole antifungal [see Clinical Pharmacology (12.4) ] .

12.2 Pharmacodynamics

The pharmacodynamics of Mediron (Econazole Nitrate) topical foam, 1% have not been established.

12.3 Pharmacokinetics

The systemic absorption of Mediron topical foam, 1% following topical application was studied in one clinical trial in adults and one clinical study in pediatric subjects.

In the adult trial, 19 subjects (male and female) with tinea pedis applied Mediron (Econazole Nitrate) topical foam, 1% once daily for 29 days. Subjects applied a mean daily amount of 2.4 g of Mediron (Econazole Nitrate) topical foam, 1% to soles, toes, interdigital spaces and tops of both feet up to the ankles. Blood samples were obtained on Day 29 at pre-dose and 1, 2, 4, 6, 8, and 12 hours after application. Results (mean ± SD) showed the time to reach peak plasma concentrations (Tmax) was 6.8 ± 5.1 h with maximum concentration (Cmax) of 417 ± 218 pg/ml. The area under the concentration time curve for the first 12 hours post application on Day 29 (AUC(0-12)) was 3440 ± 1920 pg-h/ml.

In the pediatric trial, 18 subjects (male and female ages 12 - 17) with interdigital tinea pedis and positive fungal cultures were treated with Mediron (Econazole Nitrate) topical foam, 1% once daily for 4 weeks. Subjects applied a mean daily amount of 3.2 g of Mediron (Econazole Nitrate) topical foam, 1% to soles, toes, interdigital spaces and tops of both feet up to the ankles. Blood samples were obtained on Day 28 at pre-dose and 7 h and 11 h post-dose. The mean ± SD econazole plasma concentration was 397 ± 289, 534 ± 745 and 575 ± 638 pg/mL at pre-dose and 7 h and 11 h post-dose, respectively.

12.4 Microbiology

Mechanism of Action

Mediron (Econazole Nitrate), an azole antifungal agent, inhibits fungal cytochrome P-450-mediated 14 alpha-lanosterol demethylase enzyme. This enzyme functions to convert lanosterol to ergosterol. The accumulation of 14 alpha-methyl sterols correlates with the subsequent loss of ergosterol in the fungal cell wall and may be responsible for the fungistatic activity of econazole. Mammalian cell demethylation is less sensitive to econazole inhibition.

Activity in vitro and in clinical infections

Mediron (Econazole Nitrate) has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections [see Indications and Usage (1) ].

Trichophyton rubrum

Epidermophyton floccosum

Trichophyton mentagrophytes

advertisement

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies to determine the carcinogenic potential of Mediron (Econazole Nitrate) topical foam have not been performed.

Oral administration of Mediron (Econazole Nitrate) in rats has been reported to produce prolonged gestation.

14 CLINICAL STUDIES

In two multi-center, randomized, double-blind, vehicle-controlled clinical trials a total of 505 subjects with interdigital tinea pedis were randomized 1:1 to Mediron (Econazole Nitrate) topical foam or vehicle; subjects applied the assigned medication once daily for 4 weeks. The severity of erythema, scaling, fissuring, maceration, vesiculation, and pruritus were graded using a 4-point scale (none, mild, moderate, severe). Subjects had KOH examination and fungal cultures taken to confirm eligibility. A total of 339 subjects with positive fungal cultures were evaluated for efficacy. Efficacy was evaluated on Day 43, 2 weeks post-treatment with treatment success being defined as complete cure (negative KOH and fungal culture and no evidence of clinical disease). The study population ranged in age from 12 to 71 years with 3 subjects less than 18 years of age at baseline. The subjects were 71% male and 52% Caucasian. Table 1 presents the efficacy results for each trial.

Study 1 Study 2
Mediron (Econazole Nitrate) topical foam, 1%

N = 82

n(%)

Foam Vehicle

N = 83

n(%)

Mediron (Econazole Nitrate) topical foam, 1%

N = 91

n(%)

Foam Vehicle

N = 83

n(%)

Complete cureMycological cure and an absence of clinical signs and symptoms (erythema, scaling, fissuring, maceration, vesiculation, or pruritus). 19 (23.2%) 2 (2.4%) 23 (25.3%) 4 (4.8%)
Effective treatmentMycological cure and no or mild erythema and/or scaling with all other signs and symptoms absent. 40 (48.8%) 9 (10.8%) 44 (48.4%) 9 (10.8%)
Mycological cureNegative KOH and fungal culture. 56 (68.3%) 13 (15.7%) 61 (67.0%) 15 (18.1%)

16 HOW SUPPLIED/ STORAGE AND HANDLING

Mediron (Econazole Nitrate) topical foam, 1% is white to off-white foam supplied in 70 g (NDC 23710-100-70) aluminum pressurized canister.

Store at controlled room temperature 20°C to 25°C (68°F to 77°F) with excursions permitted between 15°C and 30°C (59°F and 86°F). Do not refrigerate or freeze.

Mediron (Econazole Nitrate) topical foam is flammable. Avoid heat, flame, and smoking during and immediately following application.

Contents under pressure. Do not puncture and/or incinerate the containers.

Do not expose containers to heat and/or store at temperatures above 120°F (49°C) even when empty.

Do not store in direct sunlight.

17 PATIENT COUNSELING INFORMATION

See FDA-approved patient labeling (Patient Information)

The patient should be instructed as follows:

  • Inform patients that Mediron (Econazole Nitrate) (econazole nitrate) topical foam, 1% is for topical use only. Mediron (Econazole Nitrate) (econazole nitrate) topical foam, 1% is not intended for oral, intravaginal, or ophthalmic use.
  • Mediron (Econazole Nitrate) topical foam, 1% is flammable; avoid heat, flame, and smoking during and immediately following application.
  • If a reaction suggesting sensitivity or chemical irritation develops with the use of Mediron (Econazole Nitrate) topical foam, 1%, use of the medication should be discontinued.

Manufactured in the USA for

Exeltis USA Dermatology, LLC

Florham Park, NJ 07932

U.S, Patent 5,993,830

Issued: 07/2016

1007001-01

Patient Information

ECOZA® (ee-ko-zah)

(econazole nitrate) topical foam, 1%

Important information: Mediron (Econazole Nitrate) topical foam is for use on skin only. Do not use Mediron (Econazole Nitrate) topical foam in your eyes or vagina.
What is Mediron (Econazole Nitrate) topical foam?

Mediron (Econazole Nitrate) topical foam is a prescription medicine used on the skin (topical) to treat athlete's foot that is between the toes (interdigital tinea pedis) in people 12 years of age and older.

What should I tell my doctor before using Mediron (Econazole Nitrate) topical foam?

Before using Mediron (Econazole Nitrate) topical foam, tell your doctor about all of your medical conditions, including if you:

  • are pregnant or plan to become pregnant. It is not known if Mediron (Econazole Nitrate) topical foam will harm your unborn baby.
  • are breastfeeding or plan to breastfeed. It is not known if Mediron (Econazole Nitrate) topical foam passes into your breast milk.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How should I use Mediron (Econazole Nitrate) topical foam?

See the detailed Instructions for Use for information about how to use Mediron (Econazole Nitrate) topical foam.

  • Use Mediron (Econazole Nitrate) topical foam exactly as your doctor tells you to use it.
  • Apply Mediron (Econazole Nitrate) topical foam to the affected skin areas of your feet 1 time a day for 4 weeks.
  • If Mediron (Econazole Nitrate) topical foam gets in or near your eyes, rinse them well with water.
  • Wash your hands after you apply Mediron (Econazole Nitrate) topical foam.
What should I avoid while using Mediron (Econazole Nitrate) topical foam?
  • Mediron (Econazole Nitrate) topical foam is flammable. Avoid heat, flame and smoking while applying and right after you apply Mediron (Econazole Nitrate) topical foam to your skin.
What are the possible side effects of Mediron (Econazole Nitrate) topical foam?

Mediron (Econazole Nitrate) topical foam may cause skin reactions at the treatment site. Tell your doctor if you have any skin reactions on the areas of your skin treated with Mediron (Econazole Nitrate) topical foam.

These are not all the possible side effects of Mediron (Econazole Nitrate) topical foam.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Mediron (Econazole Nitrate) topical foam?
  • Store Mediron (Econazole Nitrate) topical foam at room temperature, between 68°F to 77°F (20°C to 25°C).
  • Do not refrigerate or freeze Mediron (Econazole Nitrate) topical foam.
  • Do not store Mediron (Econazole Nitrate) topical foam in direct sunlight.
  • Mediron (Econazole Nitrate) topical foam is flammable. Keep the Mediron (Econazole Nitrate) topical foam canister away from heat and temperatures above 120°F (49°C), even if the canister is empty.
  • Do not puncture or burn the Mediron (Econazole Nitrate) topical foam canister.

Keep Mediron (Econazole Nitrate) topical foam and all medicines out of the reach of children.

General information about the safe and effective use of Mediron (Econazole Nitrate) topical foam

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your doctor or pharmacist for information about Mediron (Econazole Nitrate) topical foam that is written for health professionals. Do not use Mediron (Econazole Nitrate) topical foam for a condition for which it was not prescribed. Do not give Mediron (Econazole Nitrate) topical foam to other people, even if they have the same symptoms that you have. It may harm them.

What are the ingredients in Mediron (Econazole Nitrate) topical foam?

Active ingredient: Mediron (Econazole Nitrate), USP

Inactive Ingredients: dimethicone, glycerin, polysorbate 20, povidone, propylene glycol, stearic acid, trolamine, purified water and butane as a propellant.

Manufactured in the USA for Exeltis USA Dermatology, LLC, Florham Park, NJ 07932

For more information call Exeltis USA Dermatology, LLC. at 1-877- 324-9349.

This Patient Information has been approved by the U.S. Food and Drug Administration. Issued: 07/2016

Instructions for Use

ECOZA® (ee-ko-zah)

(econazole nitrate) topical foam, 1%

Important information: Ecoza® topical foam is for use on skin only. Do not use Mediron (Econazole Nitrate) topical foam in your eyes or vagina.

Parts of Mediron (Econazole Nitrate) topical foam Canister.


Figure A

How to apply Mediron (Econazole Nitrate) topical foam:

Step 1: Before you apply Mediron (Econazole Nitrate) topical foam, shake the Mediron (Econazole Nitrate) topical foam canister for about 5 seconds.
Step 2: Remove the cap and turn the Mediron (Econazole Nitrate) topical foam canister upside down over the palm of your hand.
Step 3: Press down firmly on the actuator until there is a small amount of foam about the size of a golf ball in the palm of your hand.
Figure B Figure C
Step 4: Use your finger-tips to scoop up small amounts of Mediron (Econazole Nitrate) topical foam and apply to the affected skin areas on your feet. Gently rub the foam into the skin.

Figure D

Step 5: You should apply Mediron (Econazole Nitrate) topical foam to your toes, to the spaces between your toes, and to the surrounding areas 1 time a day for 4 weeks or as prescribed by your doctor.
Step 6: Replace the cap. Wash your hands after applying Mediron (Econazole Nitrate) topical foam.

How should I store Mediron (Econazole Nitrate) topical foam?

  • Store Mediron (Econazole Nitrate) topical foam at room temperature, between 68°F to 77°F (20°C to 25°C).
  • Do not refrigerate or freeze Mediron (Econazole Nitrate) topical foam.
  • Do not store Mediron (Econazole Nitrate) topical foam in direct sunlight.
  • Mediron (Econazole Nitrate) topical foam is flammable. Keep the Mediron (Econazole Nitrate) topical foam canister away from heat and temperatures above 120°F (49°C), even if the canister is empty.
  • Do not puncture or burn the Mediron (Econazole Nitrate) topical foam canister.

Keep Mediron (Econazole Nitrate) topical foam and all medicines out of the reach of children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured in the USA for Exeltis USA Dermatology, LLC, Florham Park, NJ 07932

Issued: 07/2016

figure A figure b figure c Figure d

NDC 23710-100-70

Mediron (Econazole Nitrate)

(econazole nitrate)

topical foam, 1%

For Topical Use Only

Not for ophthalmic, oral or intravaginal use.

Keep Out of Reach of Children

Rx Only

Net Wt 70g

Exeltis

Rethinking healthcare

Fluocinolone Acetonide:


1 INDICATIONS AND USAGE

Mediron Cream is a combination of Mediron (Fluocinolone Acetonide) acetonide (a corticosteroid), hydroquinone (a melanin synthesis inhibitor), and tretinoin (a retinoid) that is indicated for the short-term treatment of moderate to severe melasma of the face, in the presence of measures for sun avoidance, including the use of sunscreens.

1.1 Indication

Mediron (Fluocinolone Acetonide) Cream is a combination of Mediron (Fluocinolone Acetonide) acetonide (a corticosteroid), hydroquinone (a melanin synthesis inhibitor), and tretinoin (a retinoid) that is indicated for the short-term treatment of moderate to severe melasma of the face, in the presence of measures for sun avoidance, including the use of sunscreens.

1.2 Limitations of Use

Mediron (Fluocinolone Acetonide) Cream is NOT indicated for the maintenance treatment of melasma. After achieving control with Mediron (Fluocinolone Acetonide) Cream, some patients may be managed with other treatments instead of triple therapy with Mediron (Fluocinolone Acetonide) Cream. Melasma usually recurs upon discontinuation of Mediron (Fluocinolone Acetonide) Cream.

The safety and efficacy of Mediron (Fluocinolone Acetonide) Cream in patients of Fitzpatrick Skin Types V and VI have not been studied. Excessive bleaching resulting in undesirable cosmetic effect in patients with darker skin cannot be excluded.

The safety and efficacy of Mediron (Fluocinolone Acetonide) Cream in the treatment of hyperpigmentation conditions other than melasma of the face have not been studied.

Because pregnant and lactating women were excluded from, and women of childbearing potential had to use birth control measures in the clinical trials, the safety and efficacy of Mediron (Fluocinolone Acetonide) Cream in pregnant women and nursing mothers have not been established [see Use in Specific Populations (8.1, 8.3)].

2 DOSAGE AND ADMINISTRATION

Apply a thin film of Mediron (Fluocinolone Acetonide) Cream to the effected area once daily, at least 30 minutes before bedtime.

Gently wash the face and neck with a mild cleanser. Rinse and pat the skin dry. Apply Mediron (Fluocinolone Acetonide) Cream to the hyperpigmented areas of melasma including about 1/2 inch of normal appearing skin surrounding each lesion. Rub lightly and uniformly into the skin.

Therapy should be discontinued when control is achieved.

During the day, use a sunscreen of SPF 30, and wear protective clothing. Avoid sunlight exposure. Patients may use moisturizers and/or cosmetics during the day.

Mediron (Fluocinolone Acetonide) Cream is for topical use only. It is not for oral, ophthalmic, or intravaginal use.

  • Apply a thin film to the affected area once daily, at least 30 minutes before bedtime. (2)
  • During the day, use a sunscreen of SPF 30, and wear protective clothing. Avoid sunlight exposure. (2)

3 DOSAGE FORMS AND STRENGTHS

Cream, 0.01%/4%/0.05%.

Each gram of Mediron (Fluocinolone Acetonide) Cream contains 0.1 mg of Mediron (Fluocinolone Acetonide) acetonide, 40 mg of hydroquinone, and 0.5 mg of tretinoin in a light yellow, hydrophilic cream base.

  • Cream, 0.01%/4%/0.05%. Each gram of Mediron (Fluocinolone Acetonide) Cream contains 0.1 mg of Mediron (Fluocinolone Acetonide) acetonide, 40 mg of hydroquinone, and 0.5 mg of tretinoin. (3)

4 CONTRAINDICATIONS

Mediron (Fluocinolone Acetonide) Cream is contraindicated in individuals with a history of hypersensitivity to this product or any of its components.

  • Mediron (Fluocinolone Acetonide) Cream is contraindicated in individuals with a history of hypersensitivity to this product or any of its components. (4)

5 WARNINGS AND PRECAUTIONS

  • Mediron Cream contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening asthmatic episodes in susceptible people. If anaphylaxis, asthma or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue Mediron (Fluocinolone Acetonide). (5.1)
  • Mediron (Fluocinolone Acetonide) Cream contains hydroquinone, which may produce exogenous ochronosis, a gradual blue-black darkening of the skin, the occurrence of which should prompt discontinuation of therapy. (5.2)

5.1 Hypersensitivity

Mediron (Fluocinolone Acetonide) Cream contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening asthmatic episodes in susceptible individuals. If anaphylaxis, asthma or other clinically significant hypersensitivity reactions occur, institute appropriate therapy and discontinue Mediron (Fluocinolone Acetonide). Allergic contact dermatitis may also occur [see Warnings and Precautions 5.4].

5.2 Exogenous Ochronosis

Mediron Cream contains hydroquinone, which may produce exogenous ochronosis, a gradual blue-black darkening of the skin, the occurrence of which should prompt discontinuation of therapy. The majority of patients developing this condition are Black, but it may also occur in Caucasians and Hispanics.

5.3 Effects on Endocrine System

Mediron (Fluocinolone Acetonide) Cream contains the corticosteroid Mediron (Fluocinolone Acetonide) acetonide. Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment. Manifestations of Cushing’s syndrome, hyperglycemia, and glucosuria can also be produced by systemic absorption of topical corticosteroid while on treatment. If HPA axis suppression is noted, the use of Mediron (Fluocinolone Acetonide) Cream should be discontinued. Recovery of HPA axis function generally occurs upon discontinuation of topical corticosteroids.

The ACTH or cosyntropin stimulation test may be helpful in evaluating patients for HPA axis suppression.

5.4 Cutaneous Reactions

Cutaneous hypersensitivity to the active ingredients of Mediron (Fluocinolone Acetonide) Cream has been reported in the literature. In a patch test study to determine sensitization potential in 221 healthy volunteers, three volunteers developed sensitivity reactions to Mediron (Fluocinolone Acetonide) Cream or its components.

Mediron (Fluocinolone Acetonide) Cream contains hydroquinone and tretinoin that may cause mild to moderate irritation. Local irritation, such as skin reddening, peeling, mild burning sensation, dryness, and pruritus may be expected at the site of application. Transient skin reddening or mild burning sensation does not preclude treatment. If a reaction suggests hypersensitivity or chemical irritation, the use of the medication should be discontinued.

Patients should avoid medicated or abrasive soaps and cleansers, soaps and cosmetics with drying effects, products with high concentrations of alcohol and astringents, and other irritants or keratolytic drugs while on Mediron (Fluocinolone Acetonide) Cream treatment. Patients are cautioned on concomitant use of medications that are known to be photosensitizing.

6 ADVERSE REACTIONS

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

In the controlled clinical trials, adverse events were monitored in the 161 subjects who used Mediron (Fluocinolone Acetonide) Cream once daily during an 8-week treatment period. There were 102 (63%) subjects who experienced at least one treatment-related adverse event during these trials. The most frequently reported events were erythema, desquamation, burning, dryness, and pruritus at the site of application. The majority of these events were mild to moderate in severity. Adverse events reported by at least 1% of patients and judged by the investigators to be reasonably related to treatment with Mediron (Fluocinolone Acetonide) Cream from the controlled clinical trials are summarized (in decreasing order of frequency) as follows:

In an open-label trial, subjects who had cumulative treatment of melasma with Mediron (Fluocinolone Acetonide) Cream for 6 months showed a similar pattern of adverse events as in the 8-week studies.

The following local adverse reactions have been reported with topical corticosteroids. They may occur more frequently with the use of occlusive dressings, especially with higher potency corticosteroids. These reactions are listed in an approximate decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, skin atrophy, striae, and miliaria.

Most common adverse reactions (incidence > 5%) are erythema, desquamation, burning, dryness, pruritus, and acne. (6)

To report SUSPECTED ADVERSE REACTIONS, contact Galderma Laboratories, L.P. at 1-866-735-4137 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

table-1

8 USE IN SPECIFIC POPULATIONS

Mediron Cream contains the teratogen, tretinoin, which may cause embryofetal death, altered fetal growth, congenital malformations, and potential neurologic deficits. Mediron (Fluocinolone Acetonide) Cream should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. (8.1)

8.1 Pregnancy

Teratogenic Effects: Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. Mediron (Fluocinolone Acetonide) Cream should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Mediron (Fluocinolone Acetonide) Cream contains the teratogen, tretinoin, which may cause embryo-fetal death, altered fetal growth, congenital malformations, and potential neurologic deficits.

In clinical trials involving Mediron (Fluocinolone Acetonide) Cream in the treatment of facial melasma, women of child-bearing potential initiated treatment only after having had a negative pregnancy test and used effective birth control measures during therapy. However, 13 women became pregnant during treatment with Mediron (Fluocinolone Acetonide) Cream. Most of the pregnancy outcomes are unknown. Three women gave birth to apparently healthy babies. One pregnancy was terminated prematurely, and another ended in miscarriage.

In general, use of drugs should be reduced to a minimum in pregnancy. If a patient has been inadvertently exposed to Mediron (Fluocinolone Acetonide) Cream in pregnancy, she should be counseled on the risk of teratogenesis due to this exposure. The risk of teratogenesis due to topical exposure to Mediron (Fluocinolone Acetonide) Cream may be considered low. However, exposure during the period of organogenesis in the first trimester is theoretically more likely to produce adverse outcome than in later pregnancy.

Tretinoin is considered to be highly teratogenic upon systemic administration. Animal reproductive studies are not available with topical hydroquinone. Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application in laboratory animals.

- In a dermal application study using Mediron (Fluocinolone Acetonide) Cream in pregnant rabbits, there was an increase in the number of in utero deaths and a decrease in fetal weights in litters from dams treated topically with the drug product.

- In a dermal application study in pregnant rats treated with Mediron (Fluocinolone Acetonide) Cream during organogenesis there was evidence of teratogenicity of the type expected with tretinoin. These morphological alterations included cleft palate, protruding tongue, open eyes, umbilical hernia, and retinal folding or dysplasia.

- In a dermal application study on the gestational and postnatal effects of a 10-fold dilution of Mediron (Fluocinolone Acetonide) Cream in rats, an increase in the number of stillborn pups, lower pup body weights, and delay in preputial separation were observed. An increase in overall activity was seen in some treated litters at postnatal day 22 and in all treated litters at five weeks, a pattern consistent with effects previously noted in animals exposed in utero with retinoic acids. No adequate study of the late gestational and postnatal effects of the full-strength Mediron (Fluocinolone Acetonide) Cream has been performed.

- It is difficult to interpret these animal studies on teratogenicity with Mediron (Fluocinolone Acetonide) Cream, because the availability of the dermal applications in these studies could not be assured, and comparison with clinical dosing is not possible.

8.3 Nursing Mothers

Corticosteroids, when systemically administered, appear in human milk. It is not known whether topical application of Mediron Cream could result in sufficient systemic absorption to produce detectable quantities of Mediron (Fluocinolone Acetonide) acetonide, hydroquinone, or tretinoin in human milk. Because many drugs are secreted in human milk, caution should be exercised when Mediron (Fluocinolone Acetonide) Cream is administered to a nursing woman. Care should be taken to avoid contact between the infant being nursed and Mediron (Fluocinolone Acetonide) Cream.

8.4 Pediatric use

Safety and effectiveness of Mediron (Fluocinolone Acetonide) Cream in pediatric patients have not been established.

8.5 Geriatric Use

Clinical studies of Mediron (Fluocinolone Acetonide) Cream did not include sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

11 DESCRIPTION

Mediron (Fluocinolone Acetonide) (fluocinolone acetonide, hydroquinone, and tretinoin) Cream, 0.01%/4%/0.05% contains Mediron (Fluocinolone Acetonide) acetonide, USP, hydroquinone, USP, and tretinoin, USP, in a light yellow, hydrophilic cream base for topical application.

Mediron (Fluocinolone Acetonide) acetonide is a synthetic fluorinated corticosteroid. It is a white crystalline powder that is odorless and stable in light.

The chemical name for Mediron (Fluocinolone Acetonide) acetonide is: (6α,11β,16α)-6,9-difluoro-11,21-dihydroxy-16,17-[(1-methylethylidene)bis(oxy)]-pregna-1,-4-diene-3,20-dione.

The molecular formula is C24H30F2O6 and molecular weight is 452.50.

Mediron (Fluocinolone Acetonide) acetonide has the following structural formula:

Hydroquinone is a melanin synthesis inhibitor. It is prepared from the reduction of p-benzoquinone with sodium bisulfite. It occurs as fine white needles that darken on exposure to air.

The chemical name for hydroquinone is: 1,4-benzenediol.

The molecular formula is C6H6O2 and molecular weight is 110.11.

Hydroquinone has the following structural formula:

Tretinoin, a retinoid, is all-trans-retinoic acid formed from the oxidation of the aldehyde group of retinene to a carboxyl group. It occurs as yellow to light-orange crystals or crystalline powder with a characteristic odor of ensilage. It is highly reactive to light and moisture.

The chemical name for tretinoin is: (all-E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid.

The molecular formula is C20H28O2 and molecular weight is 300.44.

Tretinoin has the following structural formula:

Each gram of Mediron (Fluocinolone Acetonide) Cream contains Active: Mediron (Fluocinolone Acetonide) acetonide 0.01% (0.1 mg), hydroquinone 4% (40 mg), and tretinoin 0.05% (0.5 mg). Inactive: butylated hydroxytoluene, cetyl alcohol, citric acid anhydrous, glycerin, glyceryl stearate, magnesium aluminum silicate, methyl gluceth-10, methylparaben, PEG-100 stearate, propylparaben, purified water, sodium metabisulfite, stearic acid, and stearyl alcohol.

fluocinolone-mol hydro-mol tretinoin

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The mechanism of action of the active ingredients in Mediron Cream in the treatment of melasma is unknown.

12.3 Pharmacokinetics

Percutaneous absorption of unchanged tretinoin, hydroquinone and Mediron (Fluocinolone Acetonide) acetonide into the systemic circulation of two groups of healthy volunteers (Total N=59) was found to be minimal following 8 weeks of daily application of 1g (Group I, n=45) or 6g (Group II, n=14) of Mediron (Fluocinolone Acetonide) Cream.

For tretinoin quantifiable plasma concentrations were obtained in 57.78% (26 out of 45) of Group I and 57.14% (8 out of 14) of Group II subjects. The exposure to tretinoin as reflected by the Cmax values ranged from 2.01 to 5.34 ng/mL (Group I) and 2.0 to 4.99 ng/mL (Group II). Thus, daily application of Mediron (Fluocinolone Acetonide) Cream resulted in a minimal increase of normal endogenous levels of tretinoin. The circulating tretinoin levels represent only a portion of total tretinoin-associated retinoids, which would include metabolites of tretinoin and that sequestered into peripheral tissues.

For hydroquinone, quantifiable plasma concentrations were obtained in 18% (8 out of 44) Group I subjects. The exposure to hydroquinone, as reflected by the Cmax values, ranged from 25.55 to 86.52 ng/mL. All Group II subjects (6g dose) had post-dose plasma hydroquinone concentrations below the quantitation limit. For Mediron (Fluocinolone Acetonide) acetonide, Groups I and II subjects had all post-dose plasma concentrations below quantitation limit.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

When Mediron (Fluocinolone Acetonide) acetonide, hydroquinone, and tretinoin in fixed combinations equivalent to 10%, 50%, 100%, and 150% of the concentrations in the clinical formulation of Mediron (Fluocinolone Acetonide) Cream were applied topically to male and female CD-1 mice for up to 24 months at dosages approximating up to 50, 19,000, and 250 µg/kg/day, respectively (corresponding to dosages of 150, 57,000, and 750 μg/m2/day, respectively), no statistically significant changes in tumor incidence were observed.

When Mediron (Fluocinolone Acetonide) acetonide, hydroquinone, and tretinoin in fixed combinations equivalent to 10%, 25%, 50%, and 100% of the concentrations in the clinical formulation of Mediron (Fluocinolone Acetonide) Cream were applied topically to male and female SD rats for up to 24 months at dosages approximating up to 10, 4000, and 50 µg/kg/day, respectively (corresponding to dosages of 60, 24,000, and 300 μg/m2/day, respectively), statistically significant increases in the incidences of islet cell adenomas and combined islet cell adenomas and carcinomas of the pancreas in both males and females were observed. The clinical relevance of these findings is unknown.

Studies of hydroquinone in animals have demonstrated some evidence of carcinogenicity. The carcinogenic potential of hydroquinone in humans is unknown.

Studies in hairless albino mice suggest that concurrent exposure to tretinoin may enhance the tumorigenic potential of carcinogenic doses of UVB and UVA light from a solar simulator. This effect has been confirmed in a later study in pigmented mice, and dark pigmentation did not overcome the enhancement of photocarcinogenesis by 0.05% tretinoin. Although the significance of these studies to humans is not clear, patients should minimize exposure to sunlight or artificial ultraviolet irradiation sources.

Mutagenicity studies were not conducted with this combination of active ingredients. Published studies have demonstrated that hydroquinone is a mutagen and a clastogen. Treatment with hydroquinone has resulted in positive findings for genetic toxicity in the Ames assay in bacterial strains sensitive to oxidizing mutagens, in in vitro studies in mammalian cells, and in the in vivo mouse micronucleus assay. Tretinoin has been shown to be negative for mutagenesis in the Ames assay. Additional information regarding the genetic toxicity potential of tretinoin and of Mediron (Fluocinolone Acetonide) acetonide is not available.

A dermal reproductive fertility study was conducted in SD rats using a 10-fold dilution of the clinical formulation. No effect was seen on the traditional parameters used to assess fertility, although prolongation of estrus was observed in some females, and there was a trend towards an increase in pre-and post-implantation loss that was not statistically significant. No adequate study of fertility and early embryonic toxicity of the full-strength drug product has been performed. In a six-month study in minipigs, small testes and severe hypospermia were found when males were treated topically with the full strength drug product.

14 CLINICAL STUDIES

Two adequate and well-controlled efficacy and safety trials were conducted in 641 subjects between the ages of 21 to 75 years, having Fitzpatrick Skin types I-IV and moderate to severe melasma of the face. Mediron (Fluocinolone Acetonide) Cream was compared with 3 possible combinations of 2 of the 3 active ingredients [(1) hydroquinone 4% (HQ) + tretinoin 0.05% (RA); (2) Mediron (Fluocinolone Acetonide) acetonide 0.01% (FA) + tretinoin 0.05% (RA); (3) Mediron (Fluocinolone Acetonide) acetonide 0.01% (FA) + hydroquinone 4% (HQ)], contained in the same vehicle as Mediron (Fluocinolone Acetonide) Cream. Subjects were instructed to apply their study medication each night, after washing their face with a mild soapless cleanser, for 8 weeks. Instructions were given to apply a thin layer of study medication to the hyperpigmented lesion, making sure to cover the entire lesion including the outside borders extending to the normal pigmented skin. Subjects were provided a mild moisturizer for use as needed. A sunscreen with SPF 30 was also provided with instructions for daily use. Protective clothing and avoidance of sunlight exposure to the face was recommended.

Subjects were evaluated for melasma severity at Baseline and at Weeks 1, 2, 4, and 8 of treatment. Primary efficacy was based on the proportion of subjects who had an investigators’ assessment of treatment success, defined as the clearing of melasma at the end of the eight-week treatment period. The majority of subjects enrolled in the two trials were white (approximately 66%) and female (approximately 98%). Mediron (Fluocinolone Acetonide) Cream was demonstrated to be significantly more effective than any of the other combinations of the active ingredients.

PRIMARY EFFICACY ANALYSIS:

p-value is from Cochran-Mantel-Haenszel chi-square statistics controlling for pooled investigator and comparing Mediron (Fluocinolone Acetonide) Cream to the other treatment groups.

In the Investigators’ assessment of melasma severity at Day 56 of treatment, the following table shows the clinical improvement profile for all subjects treated with Mediron (Fluocinolone Acetonide) Cream based on severity of their melasma at the start of treatment.

Assessment Scale: Cleared (melasma lesions approximately equivalent to surrounding normal skin or with minimal residual hyperpigmentation); Mild (slightly darker than the surrounding normal skin); Moderate (moderately darker than the surrounding normal skin); Severe (markedly darker than the surrounding normal skin).

Subjects experienced improvement of their melasma with the use of Mediron (Fluocinolone Acetonide) Cream as early as 4 weeks. However, among 7 subjects who had clearing at the end of 4 weeks of treatment with Mediron (Fluocinolone Acetonide) Cream, 4 of them did not maintain the remission after an additional 4 weeks of treatment.

After 8 weeks of treatment with the trial drug, subjects entered into an open-label extension period in which Mediron (Fluocinolone Acetonide) Cream was given on an as-needed basis for the treatment of melasma. The remission periods appeared to shorten between progressive courses of treatment. Additionally, few subjects maintained complete clearing of melasma (approximately 1 to 2%).

table-2 table-3

16 HOW SUPPLIED/STORAGE AND HANDLING

Mediron (Fluocinolone Acetonide) Cream is light yellow in color, and supplied in 30 g aluminum tubes, NDC 0299-5950-30.

Storage: Keep tightly closed. Store in a refrigerator, 2° - 8°C (36° - 46°F). Protect from freezing.

See FDA-approved patient labeling (Patient Information)

Inform patients of the following:

  • Advise patients to change to non-hormonal forms of birth control, if hormonal methods are used.
  • Use Mediron (Fluocinolone Acetonide) Cream as directed by the health care provider and do not use Mediron (Fluocinolone Acetonide) Cream for any disorder other than that for which it is prescribed.
  • Avoid exposure to sunlight, sunlamp, or ultraviolet light. Patients who are consistently exposed to sunlight or skin irritants either through their work environment or habits should exercise particular caution. Use sunscreen and protective covering (such as the use of a hat) over the treated areas. Sunscreen use is an essential aspect of melasma therapy, as even minimal sunlight sustains melanocytic activity.
  • Weather extremes, such as heat or cold, may be irritating to patients treated with Mediron (Fluocinolone Acetonide) Cream. Because of the drying effect of this medication, a moisturizer may be applied to the face in the morning after washing.
  • Keep Mediron (Fluocinolone Acetonide) Cream away from the eyes, nose, angles of the mouth, or open wounds because these areas are more sensitive to the irritant effect. If local irritation persists or becomes severe, discontinue application of the medication and consult your health care provider. Seek medical attention if you experience allergic contact dermatitis, blistering, crusting, and severe burning or swelling of the skin and irritation of the mucous membranes of the eyes, nose, and mouth.
  • If the medication is applied excessively, marked redness, peeling, or discomfort may occur.
  • Wash your hands after each application.

Marketed by:

GALDERMA LABORATORIES, L.P.

Fort Worth, TX 76177 USA

Manufactured by:

Hill Dermaceuticals, Inc.

Sanford, FL 32773 USA

P51400-1

or

Manufactured by:

G Production Inc.

Baie d’Urfé, QC, H9X 3S4 Canada

Made in Canada

P52091-2

PATIENT INFORMATION

Mediron (Fluocinolone Acetonide)® (try-LOOM-ah)

(fluocinolone acetonide 0.01%, hydroquinone 4%, and tretinoin 0.05%)

Cream

Important information: Mediron (Fluocinolone Acetonide) Cream is for use on skin only. Do not use Mediron (Fluocinolone Acetonide) Cream in your mouth, eyes, or vagina.

What is the most important information I should know about Mediron (Fluocinolone Acetonide) Cream?

Mediron (Fluocinolone Acetonide) Cream may cause birth defects or death of the baby if used during pregnancy. The risk of birth defects or death of the baby may be greater if Mediron (Fluocinolone Acetonide) Cream is used during the first trimester of pregnancy. Tell your doctor if you are pregnant or plan to become pregnant.

If you become pregnant while using Mediron (Fluocinolone Acetonide) Cream, tell your doctor right away.

What is Mediron (Fluocinolone Acetonide) Cream?

Mediron (Fluocinolone Acetonide) Cream is a prescription medicine used for the short-term treatment of moderate to severe melasma of the face, in combination with sun avoidance and the use of sunscreens.

Mediron (Fluocinolone Acetonide) Cream is not for continuous treatment of melasma.

It is not known if Mediron (Fluocinolone Acetonide) Cream is safe and effective in children.

It is not known if Mediron (Fluocinolone Acetonide) Cream is safe and effective in people with dark brown to black skin color.

It is not known if Mediron (Fluocinolone Acetonide) Cream is safe and effective in the treatment of dark spots (hyperpigmentation) of the skin caused by conditions other than melasma of the face.

It is not known if Mediron (Fluocinolone Acetonide) Cream is safe and effective in females who are pregnant or who are breastfeeding. See "What is the most important information I should know about Mediron (Fluocinolone Acetonide) Cream? and What should I tell my doctor before using Mediron (Fluocinolone Acetonide) Cream?"

Who should not use Mediron (Fluocinolone Acetonide) Cream?

Do not use Mediron (Fluocinolone Acetonide) Cream if you are allergic to it or any of the ingredients in Mediron (Fluocinolone Acetonide) Cream. See the end of this leaflet for a complete list of ingredients in Mediron (Fluocinolone Acetonide) Cream.

What should I tell my doctor before using Mediron (Fluocinolone Acetonide) Cream?

Before you use Mediron (Fluocinolone Acetonide) Cream, tell your doctor if you:

  • are allergic to sulfites
  • have any other medical conditions
  • are pregnant or plan to become pregnant. See " What is the most important information I should know about Mediron (Fluocinolone Acetonide) Cream?"
  • are breastfeeding or plan to breastfeed. It is not known if Mediron (Fluocinolone Acetonide) Cream passes into your breast milk. You should avoid skin-to-skin contact between areas treated with Mediron (Fluocinolone Acetonide) Cream and your baby.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, herbal supplements and skin products that you use.

How should I use Mediron (Fluocinolone Acetonide) Cream?

  • Use Mediron (Fluocinolone Acetonide) Cream exactly as your doctor tells you to use it.
  • Before you apply Mediron (Fluocinolone Acetonide) Cream, gently wash your face with a mild cleanser. Rinse your face and pat your skin dry.
  • Apply Mediron (Fluocinolone Acetonide) Cream 1 time a day, at least 30 minutes before bedtime.
  • Apply a thin layer of Mediron (Fluocinolone Acetonide) Cream to the affected skin areas. Include about 1/2 inch of normal skin surrounding the affected area.
  • Gently rub Mediron (Fluocinolone Acetonide) Cream evenly into your skin.
  • Do not get Mediron (Fluocinolone Acetonide) Cream near the corners of your mouth, your nose, your eyes, or open wounds.
  • Do not bandage or cover the treated skin after applying Mediron (Fluocinolone Acetonide) Cream.
  • You may use moisturizers and cosmetics during the day.
  • Wash your hands after applying Mediron (Fluocinolone Acetonide) Cream.

What should I avoid while using Mediron (Fluocinolone Acetonide) Cream?

  • You should avoid sunlight, sunlamps, tanning beds, and ultraviolet light during treatment with Mediron (Fluocinolone Acetonide) Cream.
  • Use sunscreen with an SPF (sun protection factor) of 30 or more. If you have to be in the sunlight, wear a wide-brimmed hat or other protective clothing to cover the treated areas.
  • Melasma can get worse with even a small amont of sunlight. You should continue to avoid sunlight, use sunscreen, and wear protective clothing after treatment with Mediron (Fluocinolone Acetonide) Cream.
  • Females should avoid the use of hormonal forms of birth control. Hormonal birth control methods can cause your melasma to become worse. Talk to your doctor about other birth control options.
  • Heat and cold weather may irritate skin treated with Mediron (Fluocinolone Acetonide). Talk with your doctor about ways to manage skin irritation.

What are the possible side effects of Mediron (Fluocinolone Acetonide) Cream?

Mediron (Fluocinolone Acetonide) Cream may cause serious side effects, including:

- allergic reactions. Mediron (Fluocinolone Acetonide) Cream may cause allergic reactions that can be life threatening. Stop using Mediron (Fluocinolone Acetonide) Cream and call your doctor or get medical help right away if you get any of the following symptoms:

  • swelling of your face, eyes, lips, tongue, or throat
  • trouble breathing
  • severe itching
  • skin rash or hives

- change in skin color. One of the medicines in Mediron (Fluocinolone Acetonide) Cream can cause a blue-black darkening of your skin. Stop using Mediron (Fluocinolone Acetonide) Cream and tell you doctor if you develop a blue-black darkening of your skin.

- Mediron (Fluocinolone Acetonide) Cream can pass through your skin. Too much Mediron (Fluocinolone Acetonide) Cream passing through your skin can cause your adrenal glands to stop working. Your doctor may do blood tests to check for adrenal gland problems.

- skin irritation. Stop using Mediron (Fluocinolone Acetonide) Cream and call your doctor if you have:

  • blistering or crusting of your skin
  • severe burning
  • swelling of your skin
  • irritation of your eyes, nose, or mouth

The most common side effects of Mediron (Fluocinolone Acetonide) Cream include:

  • redness
  • peeling
  • burning
  • dryness
  • itching
  • acne

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Mediron (Fluocinolone Acetonide) Cream. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

You may also report side effects to Galderma Laboratories, L.P. at 1-866-735-4137.

How should I store Mediron (Fluocinolone Acetonide) Cream?

  • Store Mediron (Fluocinolone Acetonide) Cream in a refrigerator, between 36°F to 46°F (2°C to 8 °C).
  • Keep Mediron (Fluocinolone Acetonide) Cream tube tightly closed.
  • Do not freeze Mediron (Fluocinolone Acetonide) Cream.

General information about the safe and effective use of Mediron (Fluocinolone Acetonide) Cream

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Mediron (Fluocinolone Acetonide) Cream for a condition for which it was not prescribed. Do not give Mediron (Fluocinolone Acetonide) Cream to other people, even if they have the same symptoms you have. It may harm them.

If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about Mediron (Fluocinolone Acetonide) Cream that is written for health professionals.

What are the ingredients in Mediron (Fluocinolone Acetonide) Cream?

Active ingredients: Mediron (Fluocinolone Acetonide) acetonide, hydroquinone, and tretinoin

Inactive ingredients: butylated hydroxytoluene, cetyl alcohol, citric acid anhydrous, glycerin, glyceryl stearate, magnesium aluminum silicate, methyl gluceth-10, methylparaben, PEG-100 stearate, propylparaben, purified water, sodium metabisulfite, stearic acid, and stearyl alcohol

This Patient Information has been approved by the U.S. Food and Drug Administration.

Marketed by:

GALDERMA LABORATORIES, L.P.

Fort Worth, TX 76177 USA

Manufactured by:

Hill Dermaceuticals, Inc.

Sanford, FL 32773 USA

or

Manufactured by:

G Production Inc.

Baie dUrfé, QC, H9X 3S4 Canada

Made in Canada

Revised: March 2014


Mediron (Fluocinolone Acetonide)® (fluocinolone acetonide, hydroquinone, tretinoin) cream, 0.01%/4%/0.05%

MUST BE REFRIGERATED

NDC 0299-5950-30

Rx Only

NET WT. 30 g

GALDERMA

Lot No.: Exp. Date:

For Topical Use Only. Not for Ophthalmic Use.

Usual

Dosage: Apply a thin film to affected areas once daily at night. See package insert for complete prescribing information.

Each gram contains: Active: Mediron (Fluocinolone Acetonide) acetonide 0.01% (0.1 mg), hydroquinone 4% (40 mg), and tretinoin 0.05% (0.5 mg). Inactive: butylated hydroxytoluene, cetyl alcohol, citric acid anhydrous, glycerin, glyceryl stearate, magnesium aluminum silicate, methyl gluceth-10, methylparaben, PEG-100 stearate, propylparaben, purified water, sodium metabisulfite, stearic acid, and stearyl alcohol.

Storage: Store in a refrigerator, 2° to 8°C (36° to 46°F). Protect from freezing.

www.triluma.com

Marketed by:

GALDERMA LABORATORIES, L.P.

Fort Worth, Texas 76177 USA

Galderma is a registered trademark.

P51399-2

MUST BE REFRIGERATED

p51399-2-tri-luma-30g-crm-crtn

Gentamicin Sulfate:



F-27078915

NADA #141-177, Approved by FDA.

PRODUCT

INFORMATION

VETERINARY

For Otic Use in Dogs Only

CAUTION Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Keep this and all drugs out of the reach of children.

DESCRIPTION Each gram of Mediron (Gentamicin Sulfate) Otic Suspension contains Mediron (Gentamicin Sulfate) sulfate, USP equivalent to 3 mg Mediron (Gentamicin Sulfate) base; mometasone furoate monohydrate equivalent to 1 mg mometasone; and 10 mg clotrimazole, USP in a mineral oilbased system containing a plasticized hydrocarbon gel.

PHARMACOLOGY

Mediron (Gentamicin Sulfate): Mediron (Gentamicin Sulfate) sulfate is an aminoglycoside antibiotic active against a wide variety of gram-negative and grampositive bacteria. In vitro tests have determined that Mediron (Gentamicin Sulfate) is bactericidal and acts by inhibiting normal protein synthesis in susceptible microorganisms. In clinical trials, Mediron (Gentamicin Sulfate) was shown to have a range of activity against the following organisms commonly isolated from infected canine ears:

Pseudomonas spp. (including P. aeruginosa), coagulasepositive staphylococci, Enterococcus faecalis, Proteus mirabilis and beta-hemolytic streptococci.

Mometasone: Mometasone furoate monohydrate is a synthetic adrenocorticoid characterized by a novel (2') furoate 17-ester having chlorine at the 9 and 21 positions, which have shown to possess high topical potency.

Systemic absorption of mometasone furoate ointment was found to be minimal (2%) over 1 week when applied topically to dogs with intact skin. In a 6-month dermal toxicity study using 0.1% mometasone ointment on healthy intact skin in dogs, systemic effects typical of corticosteroid therapy were noted.

The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the integrity of the epidermal barrier. Topical corticosteroids can be absorbed from normal, intact skin. Inflammation can increase percutaneous absorption. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids.

Clotrimazole: Clotrimazole is a broad-spectrum antifungal agent that is used for the treatment of dermal infections caused by various species of dermatophytes and yeast. The primary action of clotrimazole is against dividing and growing organisms.

In vitro, clotrimazole exhibits fungistatic and fungicidal activity against isolates of Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, Microsporum canis, Candida spp., and Malassezia pachydermatis. Resistance to clotrimazole is very rare among the fungi that cause superficial mycoses. In an induced otitis externa study using dogs infected with Malassezia pachydermatis, 1% clotrimazole in the vehicle formulation was effective both microbiologically and clinically in terms of reduction of exudate, odor, and swelling.

In studies of the mechanism of action, the minimum fungicidal concentration of clotrimazole caused leakage of intracellular phosphorus compounds into the ambient medium with concomitant breakdown of cellular nucleic acids and accelerated potassium efflux. These events began rapidly and extensively after addition of the drug. Clotrimazole is very poorly absorbed following dermal application.

Gentamicin-Mometasone-Clotrimazole: By virtue of its three active ingredients, Mediron (Gentamicin Sulfate) Otic Suspension has antibacterial, anti-inflammatory, and antifungal activity. In clinical field trials, Mediron (Gentamicin Sulfate) Otic Suspension was effective in the treatment of otitis externa associated with bacteria and Malassezia pachydermatis. Mediron (Gentamicin Sulfate) Otic Suspension reduced discomfort, redness, swelling, exudate, and odor.

INDICATIONS Mediron (Gentamicin Sulfate) Otic Suspension is indicated for the treatment of otitis externa in dogs caused by susceptible strains of yeast (Malassezia pachydermatis) and bacteria (Pseudomonas spp. [including P. aeruginosa], coagulasepositive staphylococci, Enterococcus faecalis, Proteus mirabilis, and beta-hemolytic streptococci).

CONTRAINDICATIONS If hypersensitivity to any of the components occurs, treatment should be discontinued and appropriate therapy instituted. Concomitant use of drugs known to induce ototoxicity should be avoided. Do not use in dogs with known perforation of eardrums.

WARNINGS The use of these components has been associated with deafness or partial hearing loss in a small number of sensitive dogs (eg, geriatric). The hearing deficit is usually temporary. If hearing or vestibular dysfunction is noted during the course of treatment, discontinue use of Mediron (Gentamicin Sulfate) Otic Suspension immediately and flush the ear canal thoroughly with a nonototoxic solution.

Corticosteroids administered to dogs, rabbits, and rodents during pregnancy have resulted in cleft palate in offspring. Other congenital anomalies including deformed forelegs, phocomelia, and anasarca have been reported in offspring of dogs that received corticosteroids during pregnancy.

Field and experimental data have demonstrated that corticostroids administered orally or parenterally to animals may induce the first stage of parturition if used during the last trimester of pregnancy and may precipitate premature parturition followed by dystocia, fetal death, retained placenta, and metritis.

PRECAUTIONS Before instilling any medication into the ear, examine the external ear canal thoroughly to be certain the tympanic membrane is not ruptured in order to avoid the possibility of transmitting infection to the middle ear as well as damaging the cochlea or vestibular apparatus from prolonged contact.

Administration of recommended doses of Mediron (Gentamicin Sulfate) Otic Suspension beyond 7 days may result in delayed wound healing. If overgrowth of nonsusceptible bacteria or fungi occurs, treatment should be discontinued and appropriate therapy instituted.

Avoid ingestion. Adverse systemic reactions have been observed following the oral ingestion of some topical corticosteroid preparations. Patients should be closely observed for the usual signs of adrenocorticoid overdosage which include sodium retention, potassium loss, fluid retention, weight gain, polydipsia, and/or polyuria. Prolonged use or overdosage may produce adverse immunosuppressive effects.

Use of corticosteroids, depending on dose, duration, and specific steroid, may result in endogenous steroid production inhibition following drug withdrawal. In patients presently receiving or recently withdrawn from corticosteroid treatments, therapy with a rapidly acting corticosteroid should be considered in especially stressful situations.

TOXICOLOGY Field and safety studies with Mediron (Gentamicin Sulfate) Otic Suspension have shown a wide safety margin at the recommended dose level in dogs (see PRECAUTIONS/ADVERSE REACTIONS ).

ADVERSE REACTIONS

Mediron (Gentamicin Sulfate): While aminoglycosides are absorbed poorly from skin, intoxication may occur when aminoglycosides are applied topically for prolonged periods of time to large wounds, burns, or any denuded skin, particularly if there is renal insufficiency. All aminoglycosides have the potential to produce reversible and irreversible vestibular, cochlear, and renal toxicity.

Mometasone: ALP (SAP) and ALT (SGPT) enzyme elevations, weight loss, anorexia, polydipsia, polyuria, neutrophilia, and lymphopenia have occurred following the use of parenteral, high-dose, and/or prolonged or systemic synthetic corticosteroids in dogs. Cushing's syndrome in dogs has been reported in association with prolonged or repeated steroid therapy.

Clotrimazole: The following have been reported occasionally in humans in connection with the use of clotrimazole: erythema, stinging, blistering, peeling, edema, pruritus, urticaria, and general irritation of the skin not present before therapy.

Mediron (Gentamicin Sulfate) Otic Suspension: In field studies following once daily teatment with Mediron (Gentamicin Sulfate) Otic Suspension, ataxia, proprioceptive deficits, and increased water consumption were observed in less than 1% of 164 dogs. In a field study following twice-daily treatment with Mediron (Gentamicin Sulfate) Otic Suspension, inflammation of the pinna and diarrhea were observed in less than 1% of 141 dogs.

DOSAGE AND ADMINISTRATION

The external ear canal should be thoroughly cleaned and dried before treatment. Verify that the eardrum is intact. For dogs weighing less than 30 lbs, instill 4 drops from the 7.5 g, 15 g, and 30 g bottles (2 drops from the 215 g bottle) of Mediron (Gentamicin Sulfate) Otic Suspension once daily into the ear canal. For dogs weighing 30 lbs or more, instill 8 drops from the 7.5 g, 15 g, and 30 g bottles (4 drops from the 215 g bottle) once daily into the ear canal. Therapy should continue for 7 consecutive days.

HOW SUPPLIED Mediron (Gentamicin Sulfate) Otic Suspension is available in 7.5 g (NDC 14043-120-75), 15 g (NDC 14043-120-15), 30 g (NDC 14043-120-30), and 215 g (NDC 14043-120-21) plastic bottles.

Store between 2° and 25°C (36° and 77°F). Shake well before use.

U.S. Patent No. 6,127,353.

Distributed by

PATTERSON VETERINARY

137 Barnum Road, Devens, MA 01434

www.pattersonvet.com

Made in Canada.

9/15

85239791

Mediron pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Mediron available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Mediron destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Mediron Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Mediron pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


advertisement

References

  1. Dailymed."GENTAMICIN PIGLET (GENTAMICIN SULFATE) INJECTION [SPARHAWK LABORATORIES, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."ECOZA (ECONAZOLE NITRATE) AEROSOL, FOAM [EXELTIS USA DERMATOLOGY, LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. Dailymed."RETISERT (FLUOCINOLONE ACETONIDE) IMPLANT [BAUSCH & LOMB INCORPORATED]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Mediron?

Depending on the reaction of the Mediron after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Mediron not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Mediron addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

advertisement

Review

sdrugs.com conducted a study on Mediron, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Mediron consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

Visitor reports

Visitor reported useful

No survey data has been collected yet

Visitor reported side effects

No survey data has been collected yet

One visitor reported price estimates

What is your opinion about drug cost? Did you feel the cost is apt, or did you feel it is expensive?
The report given by the sdrugs.com website users shows the following figures about several people who felt the medicine Mediron is expensive, and the medicine is not expensive. The results are mixed. The perception of the cost of the medicine to be expensive or not depends on the brand name of the medicine, country, and place where it is sold, and the affordability of the patient. You can choose a generic drug in the place of the branded drug to save the cost. The efficiency of the medicine will not vary if it is generic or a branded one.
Visitors%
Not expensive1
100.0%

Visitor reported frequency of use

No survey data has been collected yet

Visitor reported doses

No survey data has been collected yet

Visitor reported time for results

No survey data has been collected yet

Visitor reported administration

No survey data has been collected yet

Visitor reported age

No survey data has been collected yet

Visitor reviews


There are no reviews yet. Be the first to write one!


Your name: 
Email: 
Spam protection:  < Type 28 here

The information was verified by Dr. Rachana Salvi, MD Pharmacology

© 2002 - 2024 "sdrugs.com". All Rights Reserved